The central theme of these investigations is the development of information concerning the protective and pathogenetic potential of vaccines within the herpesvirus group. Prior studies have established analogies between murine cytomegalovirus and human cytomegalovirus infections, and have demonstrated unusual features of attenuation and reacquisition of virulence of murine cytomegalovirus in its natural host. The proposed studies are designed to exploit this animal model to answer fundamental questions about 1) the mechanism of attenuation of cytomegaloviruses; 2) the altered pathogenicity of live, attenuated murine cytomegalovirus for mice; and 3) the possibility that human cytomegalovirus also has potential virulence lability as evidenced by lability of its genome.